rs202068829

Variant names:

• chrX-65518409-C-G
• rs202068829
• NM_031206.7:c.1505G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-65518409-C-G
• chrX-65518409-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_031206.7(LAS1L):​c.1505G>C​(p.Arg502Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R502H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 24)
• Consequence: LAS1L NM_031206.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.450
• Publications: 3 publications found

Genes affected

LAS1L (HGNC:25726): (LAS1 like ribosome biogenesis factor) Enables RNA binding activity. Predicted to be involved in maturation of 5.8S rRNA and maturation of LSU-rRNA. Located in membrane. Part of MLL1 complex. Implicated in Wilson-Turner syndrome. [provided by Alliance of Genome Resources, Apr 2022]

LAS1L Gene-Disease associations (from GenCC):

• Wilson-Turner syndrome

  Inheritance: XL Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P
• spinal muscular atrophy with respiratory distress type 2

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked syndromic intellectual disability

  Inheritance: XL Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAS1L	NM_031206.7	c.1505G>C	p.Arg502Pro	missense_variant	Exon 12 of 14	ENST00000374811.8	NP_112483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAS1L	ENST00000374811.8	c.1505G>C	p.Arg502Pro	missense_variant	Exon 12 of 14	1	NM_031206.7	ENSP00000363944.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Nov 22, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	.;T;.
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.6	.;M;.
PhyloP100		0.45
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.16	T;T;D
Polyphen		0.90	P;D;D
Vest4		0.62
MutPred		0.41		.;Gain of loop (P = 0.0045);.;
MVP		0.69
MPC		1.6
ClinPred		0.94	D
GERP RS		3.9
Varity_R		0.60
gMVP		0.82
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs202068829; hg19: chrX-64738289;